Heavy ions are riveting in radiation biophysics, particularly in the areas of radiotherapy and space radiation protection. Accelerated charged particles can indeed penetrate deeply in the human body to sterilize tumors, exploiting the favorable depth-dose distribution of ions compared to conventional X rays. Conversely, the high biological effectiveness in inducing late effects presents a hazard for manned space exploration. Even after half a century of accelerator-based experiments, clinical applications and flight research, these two topics remain both fascinating and baffling. Heavy-ion therapy is very expensive, and despite the clinical success it remains controversial. Research on late radiation morbidity in spaceflight led to a reduction in uncertainty, but also pointed to new risks previously underestimated, such as possible damage to the central nervous system. Recently, heavy ions have also been used in other, unanticipated biomedical fields, such as treatment of heart arrhythmia or inactivation of viruses for vaccine development. Heavy-ion science nicely merges physics and biology and remains an extraordinary research field for the 21st century.